Human α1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function

Hartmut Loebermann, Ryoji Tokuoka, Johann Deisenhofer, Robert Huber

Research output: Contribution to journalArticle

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Abstract

Two closely related crystal structures of α1-proteinase inhibitor modified at the reactive site peptide bond Met358-Ser359 have been analysed. The crystal structure has been obtained from diffraction data at 3 Å resolution, with phases originally from isomorphous replacement. The electron density map was substantially improved by cyclic averaging of the electron densities of the two crystal forms and allowed the chain to be traced in terms of the known chemical amino acid sequence. Energy restrained crystallographic refinement was initiated and resulted in conventional R-values of 0.251 for the tetragonal crystal form (6 to 3 Å resolution) and 0.247 for the hexagonal crystal form (6 to 3.2 Å resolution). The polypeptide chain is almost completely arranged in well-defined secondary structural elements: three β-sheets and eight α-helices. The helices are preferentially formed by the first 150 residues. They are in proximity underneath sheet A. The chain ends Met358 and Ser359 of the nicked species are arranged in strands on opposite ends of the molecule indicating a major structural rearrangement upon modification of the intact inhibitor. It is suggested that the Met358 strand is in a different conformation removed from sheet A and approaches Ser359 in the intact inhibitor species. Glu342, which is exchanged by a lysine in the Z-variant is in a strategic position for such a rearrangement. The three carbohydrate chains of α1-proteinase inhibitor have partly defined electron density close to their attachment sites at asparagine residues. The anti-thrombin and ovalbumin amino acid sequences can be accommodated in the α1 inhibitor molecular structure. The intron-exon junctions of the ovalbumin and the α1-proteinase inhibitor gene are all in surface loops of the mature protein.

Original languageEnglish (US)
Pages (from-to)531-557
Number of pages27
JournalJournal of Molecular Biology
Volume177
Issue number3
DOIs
StatePublished - Aug 15 1984

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Molecular Models
Peptide Hydrolases
Ovalbumin
Electrons
Amino Acid Sequence
Peptides
Asparagine
Molecular Structure
Thrombin
Introns
Lysine
Exons
Catalytic Domain
Carbohydrates
Genes
Proteins

ASJC Scopus subject areas

  • Virology

Cite this

Human α1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. / Loebermann, Hartmut; Tokuoka, Ryoji; Deisenhofer, Johann; Huber, Robert.

In: Journal of Molecular Biology, Vol. 177, No. 3, 15.08.1984, p. 531-557.

Research output: Contribution to journalArticle

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